Umpolung oxidative

In the oxidative Eschenmoser sulfide contraction (Scheme 11), thioamide 59 is oxidized by benzoyl peroxide to give either a symmetrical disulfide or the O-benzoate of the thiolactam-S-oxide. In any event, the once-nucleophilic thioamide sulfur atom is now forced to adopt the role of electrophile a reactivity umpolung has, in effect, been achieved.13 The nucleophilic enamide 65 attacks the sulfur atom leading to the formation of sulfur-bridged intermediate 66. The action of a phosphine or a phosphite thiophile on the putative episulfide then gives vinylogous amidine 67. 

Fermenting baker s yeast also catalyzes the 1,4-addition of a formal trifluoroethanol-d1-synthon to a,/i-unsaturated aldehydes, to give optically active l,l,l-trifluoro-2-hydroxy-5-alka-nones52. Presumably, the mechanism involves oxidation of the alcohol to the corresponding aldehyde followed by an umpolung step with thiamine pyrophosphate and Michael addition to the a,/i-unsaturated aldehyde. For example, l,l,l-trifluoro-2-hydroxy-5-hexanone (yield 26%, ee 93%) is thus obtained from trifluoroethanol and l-bnten-3-one. 

As known from the Umpolung reactions, dithioacetals can be deprotonated efficiently among others [230, 306], a recent application is 122 [307] (Scheme 1.54). Even basic aluminum oxide can catalyze these isomerizations. One older example reports the isomerization of an S-propargyl phosphanesulfide to the allene [308],... 

A synthetically very potent and unique feature of organic electrosynthesis is the oxidative or reductive Umpolung of reactivity. Reactive acceptors are anodically available as radical cations in a wide variety by the oxidative Umpolung of donors. This way two donors can be coupled in one step if one of them is converted to an acceptor at the electrode. Chemically, at least two additional... 

The principle of electrochemical redox- Umpolung has been uniquely applied in cyclization. Thereby, one of two donors in the acyclic precursor is oxidized to an acceptor, whose reaction with the donor leads to cyclization. The same holds for the cyclization by way of reduction of one out of two acceptors [15]. 

The one-electron chemistry of enols has been intensively studied by Schmit-tel [108]. He has shown that the thermodynamic stability order of the ketone tautomer and the enol tautomer in the solution phase is inverted upon one-electron oxidation [109, 110]. Therefore enols are much more easily oxidized than the corresponding ketone tautomer. Supposing that the enolization is faster than the electron transfer, it ought to be possible to oxidize the enol present in small amounts beside the ketone in the equilibrium mixture. The following cyclization reactions are as useful approach to the chemistry of enol radical cations and can be considered as the a-umpolung of ketones. 

Schmidtke H-H (1994) Vibrational Progressions in Electronic Spectra of Complex Compounds Indicating Stron Vibronic Coupling. 171 69-112 Schmittel M (1994) Umpolung of Ketones via Enol Radical Cations. 169 183-230 Schonherr T (1997) Angular Overtap Model Applied to Transition Metal Complexes and dN-Ions in Oxide Host Lattices. 191 87-152... 

From the retrosynthetic point of view, electrochemical redox reactions are an easy way to accomplish the principle of redox-umpolung (polarity reversal) [2]. As can be seen in Scheme 22.1, oxidation of an electron-rich neutral compound will lead to an electrophilic cation radical, or starting with a nucleophilic anion, anodic oxidation may lead to an electrophilic cation. In the mirror image reductions, an electron-poor neutral compound is transformed to a nucleophilic anion radical, or an electrophilic cation will end up as a nucleophilic anion. 

Conversion of Reducing Radicals into Oxidizing Ones (Umpolung) 114 ... 

Allylstannane 176 is formed by the reaction of allyl acetate with distannanes [97,98], In this reaction, umpolung of the electrophilic 7r-ally] palladium to the nucleophilic allylstannane occurs. Allylation of bromoindole 198 to give allylindole 199 involves the oxidative addition of 198 to Pd, transmetallation with the allylstannane 176, and final reductive elimination [99],... 

The anti-Markovnikov photochemical addition of malononitrile onto styrenes in the presence of lithium carbonate and a cyanoarene has been reported. In this case, excited 9-cyanophenanthrene (9-CP) oxidizes an olefin by PET, and the resultant radical cation adds to the malononitrile anion. The resulting radical is then reduced by 9-CP - and protonated to afford the end products [29]. This represents one of the rare examples involving the photoaddition of a carbanion to an olefin, and is explained by the PET-induced Umpolung of the latter, which thus becomes electrophilic. 

The current density has a dramatic influence on the yield of 52 and reveals that more than one electrode reaction is involved in the sequence. When the current density is in the range of 2.8. 7 mA/cm2, 52 is directly obtained in about 30% yield. The rationale for the formation of 52 starts with the direct or indirect generation of phenoxyl radicals at the BDD anode. Since the used conditions will provide concentrations of oxyl spin centers, which exclude a recombination, the transformation has to follow a different mechanistic course. The anodic treatment will cause an Umpolung effect because the electron rich phenol is oxidized [110-113]. Such phenoxyl species are still electrophilic despite the liberation of a proton [114-119]. The electrophilic attack occurs at the most electron rich position of the reaction partner which provides the observed connectivity in 52 (Scheme 21). 

In the case of vinyl radical cyclizations of 49E , the intermediate silacycle could be oxidized under Tamao conditions to afford ketone 51 (2) [124], The consequence is an umpolung installation of an acetyl group, with the vinyl radical serving as an acyl anion equivalent, further expanding the synthetic potential of the Si-tethered radical additions. 

Trithiocarbonate S-oxides are reactive towards alkyllithiums [111] thio-philic additions were carried out at -78 °C. The resulting carbanions, stabilised by three sulfur groups, were quenched by water or by other electrophiles to afford trithioorthoester oxides. With enones, 1,4-addition was observed elimination of an alkanesulfenic acid led to /1-oxoketenedithioace-tals which could be transformed into 4-oxoalkanethioates. This Umpolung route allows the formal use of an (alkylthio)carbonyl anion. 

In the oxidative or reductive versions of the reaction types listed above the [nucleophile, electrophile] combination is not allowed instead we use [nucleophile, nucleophile] combinations oxidatively or [electrophile, electrophile] combinations reductively [R—E, Nu-], [C=C( J-), Nu-], [R—Nu, E+] and [C=C(<5+), E+]. This principle (Umpolung see Section 1) vastly increases the number of choices available for synthetic schemes, and particularly allows for short cuts in conventional ones. Thus, the synthesis of ArOH or ArCN from ArH normally requires four steps (18), whereas the... 

Umpolung of Ketones via Enol Radical Cations Table 7. Irreversible oxidation potentials of enolates [89,151]... 

In 1990, two papers from two independent groups were published, addressing the issue of the a-Umpolung of ketones via enol radical cations. In a mechanistic study the a-methoxylation of anisylsubstituted ketones was reported in the presence of typical one-electron oxidants [170]. Other alcohols [171] and acetonitrile can equally well be used as nucleophiles. For quantitative... 

For example, addition of 2 equivalents of a nonnucleophilic base, 2,6-di-tert-butylpyridine, to the reaction system almost totally suppressed the reaction (Table 9). This proposes that acid catalyzed enolization is important for the a-Umpolung. In support of mechanism 1 the yields of the a-methoxylated products increased with decreasing oxidation strength of the oxidant (Table 10), since endergonic oxidation of the ketone 70 is slowed down (Fig. 2). On the other hand, in the presence of stronger aminium salts the ketone tautomer is oxidized which however does not lead to deprotonation in the benzylic position... 

Although the estimated oxidation potentials of the a-carbonyl radicals 90 are lower than those of the corresponding enols 86, a strong oxidant is needed to prevent radical type of reactions. According to the rates calculated on the basis of the Marcus theory [188], one-electron oxidation of the radicals can only compete with other radical processes when the electron transfer step is strongly exergonic. Thus, for radicals 90a and 90b the one-electron oxidant TTA" is too weak an oxidant, as reflected by both the yields of the a-Umpolung (Table 14) and the slow electron transfer rates (Table 13). 

In summary, these data support the proposed overall mechanistic scheme for the a-Umpolung reaction (Scheme 8), which invokes rapid deprotonation of the enol radical cations 86Should the other mechanisms (Scheme 3, mech. 4 and 5) be valid for the a-Umpolung reaction of 86 one would expect the yields to go up with less electron rich enols, since both the benzyl radical ArCH -C(OH)(OMe)CH3 and the a-hydroxy radical ArCH(OMe)-C-(OH)CH3 should be readily oxidized even for a p-chloroaryl system. In competition experiments... 

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